TY - JOUR
T1 - Conjugated eicosapentaenoic acid inhibits vascular endothelial growth factor-induced angiogenesis by suppressing the migration of human umbilical vein endothelial cells
AU - Tsuzuki, Tsuyoshi
AU - Shibata, Akira
AU - Kawakami, Yuki
AU - Nakagawa, Kiyotaka
AU - Miyazawa, Teruo
PY - 2007/3
Y1 - 2007/3
N2 - We have previously shown that conjugated eicosapentaenoic acid (CEPA), which is prepared by alkaline treatment of eicosapentaenoic acid and contains conjugated double bonds, suppresses tumor growth in vivo. In this earlier study, blood vessels were observed on the tumor surface in control mice, whereas in CEPA-treated mice, no such vessels were observed and the inner part of the tumor was discolored. These observations suggest that CEPA might suppress cancer cell growth through malnutrition due to a suppressive effect on tumor angiogenesis. In this study, the antiangiogenic effects of CEPA were investigated in vitro. CEPA at 5 μmol/L inhibited vascular endothelial growth factor (VEGF)-stimulated tube formation by human umbilical vein endothelial cells (HUVEC) (P < 0.05) and also inhibited VEGF-stimulated migration of HUVEC at a concentration of CEPA that suppressed tube formation (P < 0.05) but did not influence cell proliferation. The antiangiogenic mechanism of CEPA was investigated in vitro by measuring the secretion and expression of well-characterized angiogenic factors associated with cell migration, such as matrix metalloproteinases (MMP). CEPA at a concentration that suppressed tube formation inhibited secretion and mRNA expression of MMP2 and MMP9 in VEGF-stimulated HUVEC (P < 0.05). Our findings suggest that CEPA has potential use as a therapeutic dietary supplement for minimizing tumor angiogenesis.
AB - We have previously shown that conjugated eicosapentaenoic acid (CEPA), which is prepared by alkaline treatment of eicosapentaenoic acid and contains conjugated double bonds, suppresses tumor growth in vivo. In this earlier study, blood vessels were observed on the tumor surface in control mice, whereas in CEPA-treated mice, no such vessels were observed and the inner part of the tumor was discolored. These observations suggest that CEPA might suppress cancer cell growth through malnutrition due to a suppressive effect on tumor angiogenesis. In this study, the antiangiogenic effects of CEPA were investigated in vitro. CEPA at 5 μmol/L inhibited vascular endothelial growth factor (VEGF)-stimulated tube formation by human umbilical vein endothelial cells (HUVEC) (P < 0.05) and also inhibited VEGF-stimulated migration of HUVEC at a concentration of CEPA that suppressed tube formation (P < 0.05) but did not influence cell proliferation. The antiangiogenic mechanism of CEPA was investigated in vitro by measuring the secretion and expression of well-characterized angiogenic factors associated with cell migration, such as matrix metalloproteinases (MMP). CEPA at a concentration that suppressed tube formation inhibited secretion and mRNA expression of MMP2 and MMP9 in VEGF-stimulated HUVEC (P < 0.05). Our findings suggest that CEPA has potential use as a therapeutic dietary supplement for minimizing tumor angiogenesis.
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U2 - 10.1093/jn/137.3.641
DO - 10.1093/jn/137.3.641
M3 - Article
C2 - 17311953
AN - SCOPUS:33947175572
VL - 137
SP - 641
EP - 646
JO - Journal of Nutrition
JF - Journal of Nutrition
SN - 0022-3166
IS - 3
ER -